During the past year our research was focused on the following areas: The Interactions of Bromocriptine and Lergotrile with Dopamine and alpha-Adrenergic Receptors: The results indicate that lergotrile and bromocriptine are mixed putative agonist-antagonist with respect to the postsynaptic dopamine receptors. Lergotrile and bromocriptine at higher concentrations inhibit synaptosomal tyrosine hydroxylase activity, and reverse the apomorphine elicited enzyme inhibition. Thus, these ergot alkaloids behave as mixed agonist-antagonist also with respect to the presynaptic dopamine receptors. Strain-dependent Variations in Brain Phenylethanolamine N-Methyl Transferase Activity: Effect of Phenylethanolamine N-Methyl Transferase Inhibition on Epinephrine Levels: We have examined the PNMT activity in selected regions of the brain of Sprague Dawley rats (S.D.), W.K. and SHR's. In all three strains the PNMT activity is significantly higher in the regions containing cell bodies than in the regions containing terminals. The PNMT activity in the C1 and in the C1 surrounding regions, as well as in the C2 and in the C2 surrounding regions, is significantly higher in S.D. rats than in the W.K. or SHR's. Effect of Phenylethanolamine N-Methyltransferase and D beta H inhibition on Epinephrine Levels in the Brain. The effects of phenylethanolamine N-methyltransferase (PNMT) and dopamine-beta-hydroxylase (D beta H) inhibition of the epinephrine content in specific regions of the brain were studied. SKF 64139, a potent PNMT inhibitor, is effective in lowering brain epinephrine levels. The time course of PNMT inhibition by SKF 64139 parallels the lowering of epinephrine levels in the brain. Immunohistochemical Studies on the Localization and Distribution of Monomine Neuron Systems in the Rat Brain II. Tyrosine Hydroxylase in the Telencephalon. The TH enzyme levels seem to be much higher in the DA than in the NA nerve terminals of the forebrain which would explain the preferential demonstration of DA terminals in the forebrain using TH antiserum and the high and low TH enzyme activity in DA and NA.